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Prepulse inhibition of startle-induced reductions of accumbens dopamine [Abstract]

Geyer, M. A., Wilkinson, Lawrence Stephen ORCID:, Humby, Trevor ORCID: and Robbins, T. W. 1995. Prepulse inhibition of startle-induced reductions of accumbens dopamine [Abstract]. Biological Psychiatry 37 (9) , p. 634. 10.1016/0006-3223(95)94560-J

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Schizophrenia patients exhibit deficits in the prepulse inhibition of startle, an operational measure of the sensorimotor gating dysfunctions that may contribute to cognitive disorganization. In rats, activation of mesolimbic dopamine (DA) receptors (e.g., apomorphine, amphetamine, or intra-accumbens DA) produces similar disruptions of prepulse inhibition. These pharmacological manipulations provide useful models of the similar deficits in schizophrenia. Little is known about the dynamic responses of dopaminergic systems within the nucleus accumbens (NAC) to startling stimuli. These studies used in vivo microdialysis techniques to monitor extracellular levels of DA in the NAC of rats while they were being exposed to startling acoustic stimuli. Nine rats were prepared with guide cannulae into which 23 gauge dialysis probes were inserted 1 day prior to testing; 2-3 hr after the start of the perfusion, rats were placed into the startle chamber and exposed to a continuous 70 dB[A] background noise. Dialysis samples (2.0 mul/min) were collected at 6 min intervals. Startle pulses (120 dB[A] noise) were presented in blocks of 20 trials (each block lasted 5 min). In some blocks, an 86 dB[A] prepulse preceded each of the 20 pulses by 100 msec; 3-6 sample periods (with only background noise) intervened between stimulus-containing blocks. The order of presentation of pulse-alone or prepulse+pulse blocks was counterbalanced between animals. Monoamine and metabolite levels were measured using HPLC and electrochemical detection. During the 5-min presentations of startling stimuli, DA levels in the NAC decreased (-24.7 +/- 20.0%) relative to the immediately preceding 10-min baseline. This decrease in DA was maintained for only one additional sample period (-16.8 +/- 14.7%). By contrast, the 5-min presentation of prepulse+pulse trials failed to affect dialysate levels of NAC DA during (11.5 +/- 18.8%) or immediately after (0.1 +/- 16.4%) the stimulation. These effects were independent of the order in which the stimulus blocks were presented. Thus, startling acoustic stimuli produce significant and transient decreases in dialysate levels of DA in the NAC. Furthermore, prepulse stimuli effectively inhibit these effects of startling stimuli. Hence, in vivo microdialysis in awake rats can be used to explore the dynamic relationships between regionally specific monoamine release and both startle reactivity and prepulse inhibition.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Psychology
MRC Centre for Neuropsychiatric Genetics and Genomics (CNGG)
Neuroscience and Mental Health Research Institute (NMHRI)
Subjects: B Philosophy. Psychology. Religion > BF Psychology
R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Publisher: Elsevier
ISSN: 0006-3223
Last Modified: 21 Oct 2022 09:07

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